This paper reports a modeling approach for the scale-up of a lithium-ion polymer battery (LIPB). A comparison of the experimental discharge curves with the modeling results confirmed that the ...parameters used to model a small-scale LIPB could be applied to a large-scale LIPB provided the materials and composition of the electrodes as well as the processes for manufacturing the batteries were the same. The potential and current-density distribution on the electrodes of a LIPB were predicted as a function of the discharge time using the finite element method. In addition, the temperature distributions of the LIPB were calculated based on the modeling results of the potential and current-density distributions. The temperature distributions from the model were in good agreement with the experimental measurements.
Abstract
Heterozygous
HNF1A
gene mutations can cause maturity onset diabetes of the young 3 (MODY3), characterized by insulin secretion defects. However, specific mechanisms of MODY3 in humans remain ...unclear due to lack of access to diseased human pancreatic cells. Here, we utilize MODY3 patient-derived human induced pluripotent stem cells (hiPSCs) to study the effect(s) of a causal
HNF1A
+/H126D
mutation on pancreatic function. Molecular dynamics simulations predict that the H126D mutation could compromise DNA binding and gene target transcription. Genome-wide RNA-Seq and ChIP-Seq analyses on MODY3 hiPSC-derived endocrine progenitors reveal numerous HNF1A gene targets affected by the mutation. We find decreased glucose transporter GLUT2 expression, which is associated with reduced glucose uptake and ATP production in the MODY3 hiPSC-derived β-like cells. Overall, our findings reveal the importance of HNF1A in regulating
GLUT2
and several genes involved in insulin secretion that can account for the insulin secretory defect clinically observed in MODY3 patients.
Dysregulation of microRNA (miRNA) expression in various tissues and body fluids has been demonstrated to be associated with several diseases, including Type 2 Diabetes mellitus (T2D). Here, we ...compare miRNA expression profiles in different tissues (pancreas, liver, adipose and skeletal muscle) as well as in blood samples from T2D rat model and highlight the potential of circulating miRNAs as biomarkers of T2D. In parallel, we have examined the expression profiles of miRNAs in blood samples from Impaired Fasting Glucose (IFG) and T2D male patients.
Employing miRNA microarray and stem-loop real-time RT-PCR, we identify four novel miRNAs, miR-144, miR-146a, miR-150 and miR-182 in addition to four previously reported diabetes-related miRNAs, miR-192, miR-29a, miR-30d and miR-320a, as potential signature miRNAs that distinguished IFG and T2D. Of these microRNAs, miR-144 that promotes erythropoiesis has been found to be highly up-regulated. Increased circulating level of miR-144 has been found to correlate with down-regulation of its predicted target, insulin receptor substrate 1 (IRS1) at both mRNA and protein levels. We could also experimentally demonstrate that IRS1 is indeed the target of miR-144.
We demonstrate that peripheral blood microRNAs can be developed as unique biomarkers that are reflective and predictive of metabolic health and disorder. We have also identified signature miRNAs which could possibly explain the pathogenesis of T2D and the significance of miR-144 in insulin signaling.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective:
Metabolic profiling of small molecules offers a snapshot of physiological processes. To identify metabolic signatures associated with type 2 diabetes and impaired fasting glucose (IFG) ...beyond differences in glucose, we used mass spectrometry–based metabolic profiling.
Research Design and Methods:
Individuals attending an institutional health screen were enrolled. IFG (n = 24) was defined as fasting glucose (FG) of 6.1 to 6.9 mmol/L and 2-hour post glucose load <11.1 mmol/L or glycosylated hemoglobin <6.5%, type 2 diabetes (n = 27), FG ≥7.0 mmol/L, or 2-hour post glucose load ≥11.1 mmol/L, or glycosylated hemoglobin ≥6.5%, and healthy controls (n = 60), FG <6.1 mmol/L. Fasting serum metabolomes were profiled and compared using gas chromatography/mass spectrometry and liquid chromatography/mass spectrometry.
Results:
Compared to healthy controls, those with IFG and type 2 diabetes had significantly raised fructose, α-hydroxybutyrate, alanine, proline, phenylalanine, glutamine, branched-chain amino acids (leucine, isoleucine, and valine), low carbon number lipids (myristic, palmitic, and stearic acid), and significantly reduced pyroglutamic acid, glycerophospohlipids, and sphingomyelins, even after adjusting for age, gender, and body mass index.
Conclusions:
Using 2 highly sensitive metabolomic techniques, we report distinct serum profile change of a wide range of metabolites from healthy persons to type 2 diabetes mellitus. Apart from glucose, IFG and diabetes mellitus are characterized by abnormalities in amino acid, fatty acids, glycerophospholipids, and sphingomyelin metabolism. These early broad-spectrum metabolic changes emphasize the complex abnormalities present in a disease defined mainly by elevated blood glucose levels.
Adiponectin and leptin, two of the key cytokines secreted by adipocytes, have been shown to be associated with cardiovascular disease. However, the association of these adipocytokines with chronic ...kidney disease (CKD) is not clear. We examined the association of serum adiponectin, leptin levels and leptin to adiponectin ratio (LAR) with CKD in a population-based sample of Asian adults.
We conducted a case-control study (450 CKD cases and 920 controls matched for age, sex and ethnicity) involving Chinese and Indian adults aged 40-80 years who participated in the Singapore Epidemiology of Eye Diseases Study (2007-2011). CKD was defined as an estimated glomerular filtration rate <60 mL/min/1.73m2 from serum creatinine. Serum adiponectin and leptin levels were measured using commercially available ELISA. Odds ratio of CKD associated with elevated adiponectin and leptin levels were estimated using logistic regression models adjusted for age, gender, ethnicity, education, smoking, body mass index, diabetes, blood pressure, total and HDL cholesterol.
CKD cases had higher levels of leptin (mean SD 9.7 11.5 vs.16.9 20.2 ng/mL, p<0.0001) and adiponectin (10.4 7.4 vs. 9.2 4.2, p = 0.001) compared to controls. In multi-variable models, compared to those in the lowest quartile, the OR (95% confidence interval) of CKD among those in the highest quartile were: 6.46 (3.84, 10.88), 1.94 (1.32-2.85) and 2.88 (1.78-4.64) for leptin, adiponectin and LAR. Similar associations were also observed when adiponectin and leptin were analyzed as continuous variables. This positive association of serum adiponectin, leptin and LAR with CKD was consistently present in subgroups of gender, ethnicity, diabetes, hypertension and overweight status (all P-interaction >0.1).
Higher levels of serum adiponectin, leptin and LAR were positively associated with CKD independent of traditional risk factors in this Asian population.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The usage of modified asphalt binder in road pavements has been increasing in the past few decades. Therefore, quality control and understanding of modified asphalt binders have become an important ...issue. This study was conducted as a part of a larger study on the efficient management of these modified asphalt binders by evaluating the characteristics of asphalt binders mixed with styrene–butadiene–styrene (SBS), ethylene-vinyl acetate (EVA), and wax-based warm-mix additives using Fourier transform infrared (FTIR) analysis. For original asphalt binders modified with SBS, response wavenumbers were 700 and 966 cm−1, which means a particular wavenumber of polybutadiene and polystyrene, while in the case of binders modified with EVA, peak response wavenumbers were at 1242 and 1739 cm−1, which represents a particular wavenumbers of a single stretching bond between carbon and hydrate and a double stretching bond between carbon and oxygen. Asphalt binders modified with wax-type additives showed peak response at 730 and 1540 cm−1, which represents a double stretching bond of carbon and a single stretching bond between nitrogen and oxygen. It was also found that peak values increased as addition rates also increased. The results showed that the additives used in this study have particular wavenumbers that show peak responses even when mixed into asphalt binders. Using these characteristics of the additives, FTIR analysis confirms that it is possible to determine whether or not a binder has been modified.
Background: The kynurenine pathway (KP) is the major catabolic pathway for tryptophan degradation. The KP plays an important role as the sole de novo nicotinamide adenine dinucleotide (NAD + ) ...biosynthetic pathway in normal human physiology and functions as a counter-regulatory mechanism to mitigate immune responses during inflammation. Although the KP has been implicated in a variety of disorders including Huntington’s disease, seizures, cardiovascular disease, and osteoporosis, its role in renal diseases is seldom discussed. Summary: This review summarizes the roles of the KP and its metabolites in acute kidney injury (AKI) and chronic kidney disease (CKD) based on current literature evidence. Metabolomics studies demonstrated that the KP metabolites were significantly altered in patients and animal models with AKI or CKD. The diagnostic and prognostic values of the KP metabolites in AKI and CKD were highlighted in cross-sectional and longitudinal human observational studies. The biological impact of the KP on the pathophysiology of AKI and CKD has been studied in experimental models of different etiologies. In particular, the activation of the KP was found to confer protection in animal models of glomerulonephritis, and its immunomodulatory mechanism may involve the regulation of T cell subsets such as Th17 and regulatory T cells. Manipulation of the KP to increase NAD + production or diversion toward specific KP metabolites was also found to be beneficial in animal models of AKI. Key Messages: KP metabolites are reported to be dysregulated in human observational and animal experimental studies of AKI and CKD. In AKI, the magnitude and direction of changes in the KP depend on the etiology of the damage. In CKD, KP metabolites are altered with the onset and progression of CKD all the way to advanced stages of the disease, including uremia and its related vascular complications. The activation of the KP and diversion to specific sub-branches are currently being explored as therapeutic strategies in these diseases, especially with regards to the immunomodulatory effects of certain KP metabolites. Further elucidation of the KP may hold promise for the development of biomarkers and targeted therapies for these kidney diseases.
Recently, the handling of waste industrial resources has become an issue, and the importance of sustainable resources has increased. Among these waste industrial materials are glass wool and mineral ...wool, which are fibrous materials used as insulation materials with characteristics such as sound absorption, insulation, and non-flammability. However, after their service life, glass wool and mineral wool used for insulation are generally buried or incinerated, causing problems such as air and soil contamination. This research was conducted to examine the applicability of waste glass wool and mineral wool obtained from expired insulation as fiber reinforcement in cement concrete. The research aimed to evaluate the fresh concrete properties, strength properties, and durability properties by adding waste glass wool and waste mineral wool up to 0.5–2.0% of the cement weight. Regarding the slump and air content of fresh concrete, the results showed that the addition of waste fibers within this range did not significantly affect the air content. However, the slump decreased as the addition amount increased due to the high absorption, which is a characteristic of the fibers. In addition, the evaluation of strength revealed that the incorporation of fibers decreased the compressive strength compared to the reference concrete. However, the tensile strength increased due to the load-supporting function of the waste fibers. In the evaluation of freezing–thawing resistance and chloride ion penetration resistance, it was confirmed that the freezing–thawing resistance improved in all cases where waste glass wool was added. The chloride ion penetration resistance was found to be similar to that of the reference concrete. However, in the case of waste mineral wool, it was observed that an addition rate of more than 2.0% of fibers was required to ensure freezing–thawing resistance. As the addition rate increased, the total charge passed (permeability) increased significantly, leading to a decrease in chloride ion penetration resistance.
Lower extremity skeletal muscle mass (LESM) in Type 2 Diabetes (T2D) has been linked to adverse clinical events, but it is not known whether it is associated with cognitive difficulties. We conducted ...a cross-sectional study on 1,235 people (mean age 61.4 ± 8.0 years) with T2D under primary and secondary care in Singapore. Bioelectrical impedance analyses (BIA) measures of upper extremity skeletal muscle mass (UESM), LESM and appendicular skeletal muscle index (SMI) were related to the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) measures of cognition, in multiple linear regression. In multivariable models, tertile 1 LESM (b = -2.62 (-3.92 to -1.32)) and tertile 2 LESM (b = -1.73 (-2.73 to -0.73)), referenced to tertile 3) were significantly associated with decreased RBANS total score. Significant associations of LESM with cognitive domain performances were observed for tertile 1 (b = -3.75 (-5.98 to -1.52)) and tertile 2 (b = -1.98 (-3.69 to -0.27)) with immediate memory, and for tertile 1 (b = -3.05 (-4.86 to -1.24)) and tertile 2 (b = -1.87 (-3.25 to -0.48)) with delayed memory, and for tertile 1 (b = -2.99 (-5.30 to -0.68)) with visuospatial/constructional ability. Tertile 1 SMI (b = -1.94 (-3.79 to -0.08) and tertile 2 SMI (b = -1.75 (-3.14 to -0.37)) were also associated with delayed memory. There were no associations between UESM with cognitive performance. Lower LESM may be a useful marker of possible co-occuring cognitive dysfunction.
Recent development trends in wind power generation have increased the importance of the safe operation of wind-turbine blades (WTBs). To realize this objective, it is essential to inspect WTBs for ...any defects before they are placed into operation. However, conventional methods of fault inspection in WTBs can be rather difficult to implement, since complex curvatures that characterize the WTB structures must ensure accurate and reliable inspection. Moreover, it is considered useful if inspection results can be objectively and consistently classified and analyzed by an automated system and not by the subjective judgment of an inspector. To address this concern, the construction of a pressure- and shape-adaptive phased-array ultrasonic testing platform, which is controlled by a nanoengine operation system to inspect WTBs for internal defects, has been presented in this paper. An automatic classifier has been designed to detect discontinuities in WTBs by using an A-scan-imaging-based convolutional neural network (CNN). The proposed CNN classifier design demonstrates a classification accuracy of nearly 99%. Results of the study demonstrate that the proposed CNN classifier is capable of automatically classifying the discontinuities of WTB with high accuracy, all of which could be considered as defect candidates.
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